Identification of HN-1-Peptide Target in Head and Neck Squamous Cell Carcinoma Cells

The HN-1 module was previously reported to ensure efficient targeting of head and neck squamous cell carcinoma (HNSCC). Aim of this work was to indentify the target of HN-1. Targeting of HN-1 peptide was compared in normal epithelial cells (BEAS-2B) and in HNSCC tumor cells (SCC-25 and Detroit 562). Experimental, cell culture, cell polarity, and adhesion conditions were tested; structure models of peptides were created. Indeed, HN-1 was able to target HNSCC tumor cells in the previously published conditions. The targeting efficiency of immortalized normal epithelial cells was significantly lower. Nevertheless, in other experimental conditions the binding was less efficient and not specific. A scrambled sequence of HN-1, with altered order of amino acids showed even better targeting efficiency than HN-1. HN-1 was only uptaken in adherent cells, not in suspension. In conclusion, HN-1-peptide-targeting is not based on sequence specificity, but more on electrostatic interactions with the cell surface of the tumor cells.